ROLE OF VLA-4 AND LFA-1 IN ALLERGEN-INDUCED AIRWAY HYPERRESPONSIVENESS AND LUNG INFLAMMATION IN THE RAT

The aim of the study was to evaluate the effects of blocking the integ rins VLA-4 and LFA-1 on allergen-induced airway eosinophilia and respo nsiveness in Brown-Norway rats. Ovalbumin-sensitized rats were exposed to either aerosols of ovalbumin or saline. Airway responsiveness to m ethacholine (MCh) was determined 8 and 32 h after challenge. Cellular populations in the lung lavage and lung tissues were determined 32 h a fter allergen challenge. Total numbers of eosinophils were increased i n the lung lavage (25 ml) and the small airways/parenchyma in the oval bumin (OA)-challenged rats (4.37 x 10(6) +/- 0.71 and 15.54 x 10(6) +/ - 1.99, respectively) compared with the saline-challenged rats (0.99 x 109 +/- 0.81 and 4.84 x 10(6) +/- 2.27; p < 0.05). Animals treated wi th both anti-VLA-L1 and anti-LFA-1 mAbs and with anti-LFA-1 mAb alone had reduced numbers of eosinophils in the lung lavage(0.76 x 10(6) +/- 0.80 and 0.40 x 10(6) +/- 1.14, respectively; p < 0.05) and in the sm all airways/parenchyma (8.64 x 106 +/- 2.07 and 4.44 x 10(6) +/- 3.20; p < 0.05). Anti-VLA-4 mAb treatment alone did not alter the eosinophi ls recovered from the lung. Airway responsiveness to methacholine incr eased from 8 to 32 h in all ovalbumin-challenged rats, but treatment w ith anti-VLA-4, anti-LFA-1, or both mAbs prevented the increase in res ponsiveness. In conclusion, allergen-induced airway hyperresponsivenes s is inhibitable by blocking either VLA-4 or LFA-1 integrins and is as sociated with a lung eosinophilia that is LFA-1 dependent and VLA-4 in dependent. This suggests that eosinophils do not mediate allergen-indu ced airway hyperresponsiveness in the rat.